• The Korean Journal of Physiology and Pharmacology
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• 제10권5호
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• pp.273-282
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• 2006

The aim of the present study was to investigate the effects of R-(-)-2,10,11-trihydroxy-N-propylnoraporphine [R-(-)-TNPA], a selective agonist of dopaminergic $D_2$ receptor and S(-)-raclopride, a selective antagonist of dopaminergic $D_2$ receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(-)-TNPA $(10{\sim}100\;{\mu}M)$ perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA $(30\;{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10\;{\mu}M)$, an activator of L-type $Ca^2+$ channels and cyclopiazonic acid $(10\;{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$ were also inhibited. However, S(-)-raclopride $(1{\sim}10\;{\mu}M)$, given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(-)-raclopride $(3.0\;{\mu}M)$ in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(-)-TNP A $(30\;{\mu}M)$ and S(-)-raclopride $(3.0\;{\mu}M)$, the inhibitory responses of R(-)-TNPA $(30\;{\mu}M)$ on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(-)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(-)-raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(-)-TNPA may be mediated by stimulation of inhibitory dopaminergic $D_2$ receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(-)-raclopride is due to the blockade of dopaminergic $D_2$ receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic $D_2$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

• 약학회지
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• 제20권1호
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• pp.83-91
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• 1976

Effects of Alismatis water extract (AE) on the blood pressure were investigated in the rabbit and the dog. AE, when administered into the vein of rabbit and dog, into the lateral ventricle of rbbit, produced fall of blood pressure. The depressor response of the rabbits to intravenous AE was abolished by treatment with atropine, but not with chlorisondamine weakened the depressor effect of AE. Intravenous AE in this rabbit produced secondary elevation of the blood pressure. AE potentiated the pressor response of the rabbit to norepinephrine and tyramine, but nor to angiotensin, acetylcholine, and DMPP.

• The Korean Journal of Physiology and Pharmacology
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• 제9권4호
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• pp.223-230
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• 2005

The purpose of the present study was to examine the effect of naltrexone, an opioid antagonist, on secretion of catecholamines (CA) evoked by cholinergic nicotinic stimulation and membrane-depolarization from the isolated perfused rat adrenal gland and to establish the mechanism of its action. Naltrexone $(3{\times}10^{-6}M)$ perfused into an adrenal vein for 60 min produced time-dependent inhibition in CA secretory responses evoked by ACh $(5.32{\times}10^{-3}M)$ , high $K^+$ $(5.6{\times}10^{-2}M)$ , DMPP ($10^{-4}$ M) and McN-A-343 $(10^{-4}M)$ . Naltrexone itself did also fail to affect basal CA output. In adrenal glands loaded with naltrexone $(3{\times}10^{-6}M)$ , the CA secretory responses evoked by Bay-K-8644, an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$, were also inhibited. However, in the presence of met-enkephalin $(5{\times}10^{-6}M)$ , a well-known opioid agonist, the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Collectively, these experimental results demonstrate that naltrexone inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that this inhibitory effect of naltrexone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of $Ca^{2+}$ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.

• Biomolecules & Therapeutics
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• 제15권2호
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• pp.108-117
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• 2007

The aim of the present study was to investigate the effect of glibenclamide, a hypoglycemic sulfonylurea, which selectively blocks ATP-sensitive K$^+$ channels, on secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal glands. The perfusion of glibenclamide (1.0 mM) into an adrenal vein for 90 min produced time-dependently enhanced the CA secretory responses evoked by ACh (5.32 mM), high K$^+$ (a direct membrane depolarizer, 56 mM), DMPP (a selective neuronal nicotinic receptor agonist, 100 ${\mu}$M for 2 min), McN-A-343 (a selective muscarinic M1 receptor agonist, 100 ${\mu}$M for 2 min), Bay-K-8644 (an activator of L-type dihydropyridine Ca$^{2+}$ channels, 10 ${\mu}$M for 4 min) and cyclopiazonic acid (an activator of cytoplasmic Ca$^{2+}$-ATPase, 10 ${\mu}$M for 4 min). In adrenal glands simultaneously preloaded with glibenclamide (1.0 mM) and nicorandil (a selective opener of ATP-sensitive K$^+$ channels, 1.0 mM), the CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered to the considerable extent of the control release in comparison with that of glibenclamide-treatment only. Taken together, the present study demonstrates that glibenclamide enhances the adrenal CA secretion in response to stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization from the isolated perfused rat adrenal glands. It seems that this facilitatory effect of glibenclamide may be mediated by enhancement of both Ca$^{2+}$ influx and the Ca$^{2+}$ release from intracellular store through the blockade of K$_{ATP}$ channels in the rat adrenomedullary chromaffin cells. These results suggest that glibenclamide-sensitive K$_{ATP}$ channels may play a regulatory role in the rat adrenomedullary CA secretion.

• The Korean Journal of Physiology and Pharmacology
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• 제6권4호
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• pp.207-214
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• 2002

The present study was designed to clarify whether tacrine affects the release of catecholamines (CA) from the isolated perfused model of rat adrenal gland or not and to elucidate the mechanism of its action. Tacrine $(3{\times}10^{-5}{\sim}3{\times}10^{-4}\;M)$ perfused into an adrenal vein for 60 min inhibited CA secretory responses evoked by ACh $(5.32{\times}10^{-3}\;M),$ DMPP (a selective neuronal nicotinic agonist, $10^{-4}$ M for 2 min) and McN-A-343 (a selective muscarinic M1-agonist, $10^{-4}$ M for 2 min) in relatively dose- and time- dependent manners. However, tacrine failed to affect CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M).$ Tacrine itself at concentrations used in the present experiments did not also affect spontaneous CA output. Furthermore, in the presence of tacrine $(10^{-4}\;M),$ CA secretory responses evoked by Bay-K-8644 (an activator of L-type $Ca^{2+}$ channels, $10^{-4}\;M),$ but not by cyclopiazonic acid (an inhibitor of cytoplasmic $Ca^{2+}-ATPase,\;10^{-4}\;M),$ was relatively time-dependently attenuated. Also, physostigmine $10^{-4}\;M),$ given into the adrenal gland for 60 min, depressed CA secretory responses evoked by ACh, McN-A-343 and DMPP while did not affect that evoked by high $K^+.$ Collectively, these results obtained from the present study demonstrate that tacrine greatly inhibits CA secretion from the perfused rat adrenal gland evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by direct membrane-depolarization. It is suggested that this inhibitory effect of tacrine may be exerted by blocking both the calcium influx into the rat adrenal medullary chromaffin cells without $Ca^{2+}$ release from the cytoplasmic calcium store, that is relevant to the cholinergic blockade. Also, the mode of action between tacrine and physostigmine in rat adrenomedullary CA secretion seems to be similar.

• Archives of Pharmacal Research
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• 제28권6호
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• pp.699-708
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• 2005

The present study was designed to investigate the effect of naloxone, a well known opioid antagonist, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal glands, and to establish its mechanism of action. Naloxone ($10^{-6}\~10^{-5}$ M), perfused into an adrenal vein for 60 min, produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh ($5.32\times10^{-3}$ M), high K+ ($5.6\times10^{-2}$ M), DMPP ($10^{-4}$ M) and McN-A-343 ($10^{-4}$ M). Naloxone itself also failed to affect the basal CA output. In adrenal glands loaded with naloxone ($3\times10^{-6}$ M), the CA secretory responses evoked by Bay-K-8644, an activator of L-type $Ca^{2+}$ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, were also inhibited. In the presence of met-enkephalin ($5\times10^{-6}$ M), a well known opioid agonist, the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Taken together, these results suggest that naloxone greatly inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that these inhibitory effects of naloxone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of $Ca^{2+}$ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.

• Biomolecules & Therapeutics
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• 제9권3호
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• pp.201-208
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• 2001

The present study was conducted to examine the effects of cholinergic stimulation and membrane depolarization on secretion of epinephrine (EP) and norepinephrine (NE) in the perfused model of the rat adrenal gland and to investigate the effect of bromocriptine on secretion of EP and NE evoked by these secreta-gogues. Acetylcholine (ACh, 5.32 mM), high $K^{+}$(56mM), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP, 100 $\mu$M for 2 min), (3-(m-cholro-phenyl-carbamoyl-oxy)-2butynyl trimethyl ammonium chloride (McN-A-343, 100 $\mu$M for 2 min), cyclopiazonic acid (10 $\mu$M for 4 min) and methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) -pyridine-5-carboxylate (Bay-K-8644, 10 $\mu$M for 4 min) evoked a 1.3~5.3-fold greater secretion of EP than NE in the perfused rat adrenal gland. The perfusion of bromocriptine (1-10 $\mu$M) into an adrenal vein for 20 min produced relatively dose-dependent inhibition in secretion of EP and NE evoked by ACh, high $K^{+}$, DMPP, and McN-A-343. Moreover, under the presence of bromocriptine (1~10 $\mu$M), releasing responses of EP and NE evoked by cyclopiazonic acid and Bay-K-8644 were also greatly reduced. Taken together, these results suggest that cholinergic stimulation and membrane depolarization enhance more release of EP than NE in the perfumed rat adrenal medulla, and that bromocriptine inhibits the release of EP and NE evoked by stimulation of cholinergic receptors as well as by membrane depolarization. It seems that this inhibitory effect of bromocriptine is associated with inhibition of calcium channels through activation of dopaminergic D2-receptors located in the rat adrenomedullary chromaffin cells.lls.

• Natural Product Sciences
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• 제13권1호
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• pp.68-77
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• 2007

The aim of the present study was to examine the effects of green tea extract (CUMS6335) on the release of CA evoked by cholinergic stimulation and direct membrane-depolarization in the perfused model of the adrenal gland isolated from the spontaneously hypertensive rats (SHRs), and to establish the mechanism of action. Furthermore, it was also to test whether there is species difference between animals, and between CUMS6335 and EGCG, one of biologically the most powerful catechin compounds found in green tea. CUMS6335 $(100\;{\mu}g/ml)$, when perfused into an adrenal vein for 60 min, time-dependently inhibited the CA secretory responses evoked by ACh (5.32mM), high $K^+$(56 mM), DMPP $(100\;{\mu}M)$, and McN-A-343 $(100\;{\mu}M)$ from the isolated perfused adrenal glands of SHRs. However, CUMS6335 itself did fail to affect basal catecholamine output. Also, in adrenal glands loaded with CUMS6335 $(100\;{\mu}g/ml)$, the CA secretory responses evoked by Bay-K-8644 $(10\;{\mu}M)$ and cyclopiazonic acid $(10\;{\mu}M)$ were also inhibited in a relatively time-dependent fashion. However, in the Presence of EGCG $(8.0\;{\mu}g/ml)$ for 60 min, the CA secretory response evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were not affected except for last period. Collectively, these results indicate that CUMS6335 inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by direct membrane-depolarization from the perfused adrenal gland of the SHR. It seems that this inhibitory effect of CUMS6335 is exerted by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of $Ca^{2+}$ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself. It seems likely that there is much difference in mode of the CA-releasing action between CUMS6335 and EGCG.

• Biomolecules & Therapeutics
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• 제17권1호
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• pp.32-42
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• 2009

The purpose of the present study was to examine the effect of dihydrexidine, a full $D_1$ receptor agonist, on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland, and to establish its mechanism of action. Dihydrexidine (10-100 ${\mu}M$), perfused into an adrenal vein for 60 min, relatively produced dose- and time-dependent inhibition in the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Dihydrexidine itself did fail to affect basal CA output. Also, in adrenal glands loaded with dihydrexidine (30 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$), an activator of L-type $Ca^{2+}$ channels, cyclopiazonic acid (10 ${\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase, and veratridine, an activator of voltage-dependent $Na+$ channels (10 ${\mu}M$), were also markedly inhibited, respectively. However, in the simultaneous presence of dihydrexidine (30 ${\mu}M$) and R (+)-SCH23390 (a selective antagonist of $D_1$ receptor, 3 ${\mu}M$), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory responses by dihydrexidinetreatment alone. In conclusion, these experimental results suggest that dihydrexidine significantly inhibits the CA secretion evoked by cholinergic stimulation (both nicotinic and muscarinic receptors) and membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of dihydrexidine may be mediated by inhibiting influx of both $Ca^{2+}$ and $Na^+$ into the cytoplasm as well as by suppression of $Ca^{2+}$ release from cytoplasmic calcium store through activation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells.

• The Korean Journal of Physiology and Pharmacology
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• 제11권5호
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• pp.197-206
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• 2007

The aim of the present study was to investigate the effects of 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine(SKF81297), a selective agonist of dopaminergic $D_1$ receptor, on the secretion of catecholamines(CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal gland, and also to elucidate the mechanism involved. SKF81297($10{\sim}100{\mu}M$) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh(5.32 mM), high $K^+$(56 mM), DMPP($100{\mu}M$) and McN-A-343($100{\mu}M$). Also, in adrenal glands loaded with SKF81297($30{\mu}M$), the CA secretory responses evoked by Bay-K-8644($10{\mu}M$), an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid($10{\mu}M$), an inhibitor of cytoplasmic $Ca^{2+}$-ATPase were also inhibited. However, in the presence of the dopamine $D_1$ receptor antagonist, (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7-ol(SCH23390, $3{\mu}M$), which is a selective antagonist of dopaminergic $D_1$ receptor, the inhibitory responses of SKF81297($30{\mu}M$) on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Collectively, these experimental results suggest that SKF81297 inhibits the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation(both nicotininc and muscarinic receptors) and membrane depolarization. This inhibitory of SKF81297 seems to be mediated by stimulation of dopaminergic $D_1$ receptors located on the rat adrenomedullary chromaffin cells, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that the presence of the dopaminergic $D_1$ receptors may be involved in regulation of CA release in the rat adrenal medulla.